BDNF-TrkB signaling through [Erk1/2.sup.MAPK] phosphorylation mediates the enhancement of fear memory induced by glucocorticoids

Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the [Erk1/2.sup.MAPK] signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted ([GR.sup.NesCre]). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of [Erk1/2.sup.MAPK] responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNF-TrkB-[Erk1/2.sup.MAPK] signaling pathways as one of the core effectors of stress-related effects of GC. Molecular Psychiatry (2014) 19, 1001-1009; doi:10.1038/mp.2013.134; published online 15 October 2013 Keywords: brain-derived neurotrophic factor; contextual fear memory; extracellular signal-regulated kinases 1/2 mitogen-activated protein kinase; glucocorticoids; tissue plasminogen activator; tropomyosin-related kinase B